A marked contrast between serotonergic and dopaminergic changes in dopa-responsive dystonia.
NEUROLOGY(2016)
摘要
Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of levodopa.(1) Autosomal dominant DRD is caused by mutations in GCH1, which encodes GTP cyclohydrolase 1 (GTPCH), the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4; the cofactor for phenylalanine and tyrosine and tryptophan hydroxylases [TH and TPH]).(1) Recently, the phenotype of this major form of DRD (GTPCH-deficient DRD) was expanded to include nonmotor symptoms, such as depression, anxiety, and obsessive-compulsive disorder, and these psychiatric symptoms were attributed to serotonin deficiency.(2,3) However, the actual status of brain serotonergic involvement in GTPCH-deficient DRD is unknown. To evaluate possible serotonin deficiency, we measured levels of serotonin markers in the striatum (one of the serotonin- and dopamine-rich brain regions)(4) in a 19-year-old woman with DRD and a GCH1 nonsense mutation.(5) Her dystonia (onset at 5 years of age) was well controlled by levodopa (without a decarboxylase inhibitor) 750 mg/d for 11 years (no psychiatric symptoms and residual motor signs) until her automobile accidental death. Neuropathologic studies revealed a normal population of cells with reduced melanin in the substantia nigra and also no evidence of degeneration in other brain areas.(1,5) This study was approved by the institutional review board of the Centre for Addiction and Mental Health.
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